A novel series of macrocyclic FXIa inhibitors was designed based on our lead acyclic phenyl
imidazole chemotype. Our initial macrocycles, which were double-digit nanomolar FXIa …

Factor XIa (FXIa) inhibitors are promising novel anticoagulants, which show excellent
efficacy in preclinical thrombosis models with minimal effects on hemostasis. The discovery …

This manuscript describes the discovery of a series of macrocyclic inhibitors of FXIa with oral
bioavailability. Assisted by structure based drug design and ligand bound X-ray crystal …

Oral factor XIa (FXIa) inhibitors may provide a promising new antithrombotic therapy with an
improved benefit to bleeding risk profile over existing antithrombotic agents. Herein, we …

A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the
crystal structures of the acyclic phenylimidazole compounds. Further optimization using …

Optimization of macrocyclic inhibitors of FXIa is described which focused on modifications to
both the macrocyclic linker and the P1 group. Increases in potency were discovered through …

Compound 2 was previously identified as a potent inhibitor of factor XIa lacking oral
bioavailability. A structure-based approach was used to design analogs of 2 with novel P1 …

Antithrombotic agents that are inhibitors of factor XIa (FXIa) have the potential to
demonstrate robust efficacy with a low bleeding risk profile. Herein, we describe a series of …

Factor XIa (FXIa) is an enzyme in the coagulation cascade thought to amplify thrombin
generation but has a limited role in hemostasis. From preclinical models and human …

Abstract A series of 4, 4-disubstituted proline analogs were designed, synthesized, and
tested for selective inhibition of blood coagulation factor XIa in search of new non-vitamin K …